Classification of early and late stage Liver Hepatocellular Carcinoma patients from their genomics and epigenomics profiles.

Abstract

BackgroundLiver Hepatocellular Carcinoma (LIHC) is the second major cancer worldwide, responsible for millions of premature deaths every year. Prediction of clinical staging is vital to implement optimal therapeutic strategy and prognostic prediction in cancer patients. However, to date, no method has been developed for predicting stage of LIHC from genomic profile of samples.\n\nResultsIn current study, in silico models have been developed for classifying LIHC patients in early and late stage using RNA expression and DNA methylation data. The Cancer Genome Atlas (TCGA) dataset contains 173 early and 177 late stage samples of LIHC, was extensively analysed to identify differentially expressed RNA transcripts and methylated CpG sites that can discriminate early and late stages of LIHC samples with high precision. Naive Bayes model developed using 51 features that combine 21 CpG methylation sites and 30 RNA transcripts achieved maximum MCC 0.58 with accuracy 78.87% on validation dataset. Further, we also analysed genomics and epigenomics profiles of normal and LIHC samples and developed model to classify LIHC samples with AUROC 0.99. In addition, multiclass models developed for classifying samples in normal, early and late stage of cancer and achieved accuracy of 76.54% and AUROC of 0.86.\n\nConclusionOur study reveals stage prediction of LIHC samples with high accuracy based on genomics and epigenomics profiling is a challenging task in comparison to classification of LIHC and normal samples. Comprehensive analysis, differentially expressed RNA transcripts, methylated CpG sites in LIHC samples and prediction models are available from CancerLSP (http://webs.iiitd.edu.in/raghava/cancerlsp/).